p-Toluenesulfonic acid → 4-(2-Methyl-8-azabicyclo[3.2.1]oct-8-yl)naphthalene-1-carbonitrile

HRID 916348Notes

Reaction equation

[CH3:1][CH:2]1[C:8](=O)[CH2:7][CH:6]2[N:10]([C:11]3[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[C:14]([C:21]#[N:22])=[CH:13][CH:12]=3)[CH:3]1[CH2:4][CH2:5]2.C1(C)C=CC(S(NN)(=O)=O)=CC=1.C([BH3-])#N.[Na+].S1(CCCC1)(=O)=O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(O)C.O.C1CCCCC1.CN(C)C=O>[CH3:1][CH:2]1[CH2:8][CH2:7][CH:6]2[N:10]([C:11]3[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[C:14]([C:21]#[N:22])=[CH:13][CH:12]=3)[CH:3]1[CH2:4][CH2:5]2

Participants

Conditions

Temperature: 110 °C

Procedure

159JP84 (115 mg, 0.40 mmol) and p-toluenesulfonhydrazide (90 mg, 0.48 mmol) in absolute ethanol (1.0 mL) were refluxed overnight and the resulting white precipitate was filtered off, dried in vacuo and added to a vial containing sodium cyanoborohydride (101 mg, 1.60 mmol), N,N-dimethylformamide (2.0 mL), sulfolane (2.0 mL), p-toluenesulfonic acid (25 mg) and cyclohexane (2.0 mL). The resulting solution was heated at 110° C. for 2 days, poured into water (200 mL), extracted with ethyl acetate (2×200 mL), dried over Na2SO4, filtered, concentrated in vacuo and purified by preparative TLC (ethyl acetate/n-heptane 1:5, 5× eluted) to afford the title compound (25.3 mg, 22%) as thick oil.

Workup

filtrationthe resulting white precipitate was filtered off
customdried in vacuo
additionadded to
extractionextracted with ethyl acetate (2×200 mL)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
custompurified by preparative TLC (ethyl acetate/n-heptane 1:5, 5× eluted)

Sources & evidence

ORD record: ord-f54ceb6eab274363b2520803b0fb83a9
Source dataset: uspto-grants-2007_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07268232B2

Reaction notes

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